Will a novel drug called a PARP inhibitor make an established chemotherapy regimen more effective at controlling metastasized pancreatic cancer?
Researchers are studying how effective a new drug combination is for people with metastatic or advanced pancreatic cancer. Participants in this clinical trial must have the BRCA mutation or a known history of breast or ovarian cancer.
Standard Treatment Plus a PARP Inhibitor
The treatment in the trial uses a modified FOLFOX regimen and adds a new type of drug called a PARP inhibitor. FOLFOX is FOL (leucovorin calcium, or folinic acid), F (fluorouracil, or 5-FU), and OX (oxaliplatin). 5-FU is an antimetabolite that disrupts a specific part of the cell replication cycle. Because it targets all cells, not just cancer cells, it causes uncomfortable but manageable side effects. Leucovorin, which is derived from folic acid, enhances the effects of 5-FU. Oxaliplatin is a platinum compound that disrupts the DNA-replication process and kills cancer cells.
The PARP enzyme is important in repairing small breaks in single DNA strands. Drugs that block the action of PARP—inhibitors like ABT-888 (veliparib), the drug in this study—make the enzyme less effective at repairing the small breaks. When the DNA makes copies of itself, or replicates, these breaks in the strands are also copied and not functional, which causes the cell to die. Cancer cells replicate their DNA more often than normal cells, which is why PARP inhibitors can be an effective part of cancer treatment.
The Role of BRCA
BRCA mutations are mostly inherited, and most common in Ashkenazi Jews, Norwegian, Dutch, and Icelandic people. BRCA1 and BRCA2 genes normally function as tumor suppressor proteins and these genes make sure that damaged DNA is repaired properly. When the BRCA genes are mutated, DNA does not get repaired properly, leading to more mutations and increasing the likelihood of developing cancer. People carrying BRCA1 and BRCA2 mutations are at increased risk of developing breast, ovarian, and pancreatic cancer.
Because the DNA of BRCA carriers does not get properly repaired, PARP inhibitors may work particularly well on their cancers.
All participants will receive the experimental treatment in this trial.
We encourage you to consult your physicians for clinical trials that may be right for you. The website ClinicalTrials.gov provides more details about this trial as well as many others. You can visit the EmergingMed Trial Finder for a listing of all active pancreatic cancer clinical trials.